Experimental therapy of HPV16 induced tumors with IL12 expressed by recombinant vaccinia virus in mice

Recombinant vaccinia viruses derived from strain Praha, clone P13, and strain MVA were used for intratumoral delivery and expression of 11-12 genes in tumors induced by HPV16 E6+E7 oncogenes in mice. Intratumoral injection of 10(3) PFU of P13-IL12 virus resulted in an increase of intratumoral IL12 on days 6-13, while only low levels of IL12 were found in sera. After the inoculation of 101 PFU of MVA-IL 12, the same levels of IL12 were found as in animals injected with control virus. The intratumoral inoculation of 101 PFU P13-IL12 resulted in only approximately 30% of the tumors being virus positive, which was a consequence of reduced multiplication of the recombinant virus in vivo. The number of virus-positive tumors was not increased by repeated inoculations on three consecutive days. Intratumoral therapy with a dose of 103 PFU of P13-IL12 slowed down the growth of TC1 tumors, but never caused their regression. When local P13-IL12 treatment was combined with antigen-specific, DNA-vaccination therapy, no synergy between the two treatments was observed. The treatment with IL12-expressing virus retarded tumor growth to some degree, but did not change the number of regressing tumors. The highest efficacy of intratumoral P13-IL12 therapy was observed when the TC-1/A9 cell subline, with downregulated MHC class I expression, was used. TC-1/A9 tumors are less refractory to treatment with 10(3) P13-IL12/EL than are parental TC-1 cells.